The goal of this predoctoral training program is to provide students with the intellectualand technical skills required to solve important and complex biological problems that can be most effectively addressed by studies at the chemistry-biology interface, and to create a group of graduating chemists and biologists who can effectively communicate and function successfully in multidisciplinaryteams. The focus of the training program will be mechanistic chemistry of proteins, which is a theme that is of special interest to a significant population of faculty and students on campus, and provides an excellent model system for the application of chemical tools to solve important biological problems. The Program will involve 27 participatingfaculty from The Wistar Institute and two separate Schools within the University of Pennsylvania, The School of Medicine and The School of Arts and Sciences. Participating students will come primarily from two graduate groups that span institutionand school boundaries, the Graduate Group in Chemistry and the Graduate Group in Biochemistry and Biophysics. To insure that students carry out research within the scope of the training program, students will be selected for the program after they have chosen a thesis laboratory and project and generally within their second or third year. To insure cross-fertilization between the chemistry and biology students, those selected for support by the training grant will also participate in the following activities: (1) A course curriculum that crosses the chemistry-biology academic boundary and centers around the mechanistic chemistry of proteins, (2) A student run speaker-invited seminar and symposia series centered around the chemistry-biology interface, (3) An annual Chemistry-Biology Interface Symposia in which students interact and formally present their work to each other and other trainees, and (4) A monthly luncheon in which students and faculty informally discuss their research among themselves. The program will also adopt plans for the recruitment of underrepresented minorities and for student instruction in the responsible conduct of research. We request funds for a steady state predoctoral training group of 6 students with 3-4 years of support each. A training committee will be comprised of roughly equal representation from the three participating programs and will meet monthly. The training committee will be responsible for selecting students for training slot positions, insure equitable distributionof students, encourage application from underrepresented minorities and administer other functions of the grant.